2.1. Tumor Cell Antigens and Anti-tumor Antibodies
Tumor cells express certain antigens which are absent from, or present in small amounts on, their normal cellular counterparts. Most of these are differentiation antigens, shared by the tumor and certain embryonic cells. Some of the antigens that appear with sufficient selectivity in tumors may serve as possible targets for therapeutic agents. This has been recently reviewed for malignant melanoma, which is one of the human tumors most studied in this respect (Hellstrom and Hellstrom, in Accomplishments in Cancer Research-194 Prize Year, General Motors Cancer Research Foundation, J. G. Fortner & J. E. Rhoads, eds., J. B. Lippincott Company, Philadelphia 1985, p 216-240, as well as for other tumors (Burchell and Taylor-Papadimitriou, in R. W. Baldwin and V. S. Byers, eds., Monoclonal Antibodies for Tumor Detection and Drug Targeting, Academic Press, 1985, pp. 1-15; Kemshead, ibid, pp. 281-302).
Many antibodies have been made to cell surface antigens that are expressed in greater quantities by human tumors than by normal tissues. It has also been well established that antibodies to cell surface antigens can be cytotoxic to tumor cells in the presence of complement (Hellstrom et al., 1962, Progr. Allergy 9: 158-245), and that some antibodies can mediate antibody-dependent cellular cytotoxicity (Perlmann et al., 1969, Adv. Immunol. 11: 117-193; MacLennan et al., 1969, Immunol. 17: 897-910; Skurzak et al., 1972, J. Exp. Med. 135: 997-1002; Pollack et al., 1972, Int. J. Cancer, 9: 316-323). In the first case, an appropriate source of complement (generally rabbit or guinea pig), and in the latter case a source of effector cells (generally of mouse origin) is needed.
The evidence that antibodies to tumor-associated antigens can kill human tumor cells in the presence of human effector cells is more recent (Hellstrom et al., 1981, Int. J. Cancer 27: 281-285; as is the evidence that antibodies to such antigens can kill tumor cells in the presence of human serum as a source of complement (Hellstrom et al., 1985, Proc. Natl. Acad. Sci. 82: 1499-1502; Hellstrom et al., 1985, Monoclonal Antibodies and Cancer Therapy, USCLA Symposia on Molecular and Cellular Biology, Vol. 27, pp.149-164 Alan R. Liss, Inc., N.Y.).